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Normal and Abnormal Embryology of the Female Genital Tract

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1 Normal and Abnormal Embryology of the Female Genital Tract
Professor Hassan Nasrat Chairman Department f Obstetrics and Gynecology (Fourth Year Medical Students)

2 Definitions: Sexual determination and differentiation
Abnormalities that might affect normal differentiation of the female genital tract. Clinical complication and presentation of abnormal differentiation of the female genital tract. Development of the Internal genital system (Duct system differentiation) External Genital differentiation: Anomalies of the external genital organs: Anomalies of the internal genital tract "Müllerian anomalies“ Complications and Clinical Presentations of internal genital tract "Müllerian anomalies“

3 The mechanism of normal sexual determination and differentiation
Genetic Sex Gonadal Sex Internal Genital Sex External Genital Sex Each of the three major elements of the genital tract goes through two phases: a Bipotential phase (undifferentiated phase) Differentiation phase into either a male or female organs.

4 Embryology of The Genital Tract (Mechanism of sexual determination and differentiation)
Sexual determination: is related to the development of the primary gonad (or gonadal sex) Sexual differentiation: encompasses the events subsequent to gonadal Sex

5 (Gonadal Sex) The Development of the Gonads
The phase of indifferent gonads (Genital Ridge): The germ cells (primordial germ cells) migrate to the genital ridge by the 6th week. The germ cells influence development of the gonad into ovary or testes The covering epithelium proliferates and sends cluster of cells into the underlying mesoderm known as the cells of the sex cords. The three elements of the gonads which are still "indifferent" are now completed; the germ cells, the cells of the sex cords (the potential granulosa or Sertoli cells), and the mesenchymal stroma (potential theca/Leydig cells).

6 The phase of The phase of Gonadal Determination
Differentiate into testis or ovaries depending on the presence or absence of the Y chromosome in the germ cells. The differentiation of the gonads into testis depends on the presence of sex determining region or gene (SRY) located on the short arm of the Y chromosome Deletion of this SRY gene results in XY female. Similarly translocation of this gene to an X chromosome results in an XX male. Ovarian Differentiation Occur in the the absence of Y chromosome and SRY protein it occurs two weeks later (about the 8th week). Testis Differentiation Seminephrous tubules: proliferation of primitive sex cords The tunic albuginea The cortical region (the surface) of the testis The epididymis made by the Mesonephric tubule

7 The cortical zone that contain the germ cells develop to a much greater extent, while the medulla regress. By the fourth month: each germ cell, now become known as Oogonia, is surrounded by a single layer of epithelial cells The oogonia are transformed into primary oocytes as they enter the 1st meiotic division and arrest in prophase until puberty and beginning of ovulation. Around the 20th week of gestation the ovary contains about 7 million germ cells (see chapter on ovulation). Degeneration and atresia begins around 20 weeks and by birth approximately 20 million germ cells remain.

8 Differentiation of the Genital Ducts (The Internal Genital Organs)
The Indifferent stage: The Mesonephric (Wolffian) duct: run on either side of the primitive gut as a longitudinal ridge, covered by the coelomic epithelium. The Mullerian duct (Paramesonephric ducts): runs lateral to the Mesonephric duct. It develops, as a longitudinal invagination of coelomic epithelium that runs caudally as a solid cord cells. At its caudal part the Mullerian ducts pass medially across the front of the Wolffian ducts. The Mullerian ducts, from each side, meet and fuse as a single solid rod of cells. They further extend caudally until they make contact with the urogenital sinus; produce a prominent elevation in its posterior wall, known as the Mullerian tubercle.

9 Stage of Ductal differentiation (8 weeks):
Differentiation of male internal organs the Mullerian Inhibiting Hormone (MIH) (Sertoli cells ): responsible for regression of the ipsilateral paramesonephric ducts Testosterone (Leydig cells) responsible for development of the mesonephric duct into the male internal genitalia Differentiation of Female Internal Organs In the absence of testes (MIF and testosterone) the mesonephric system regress and the Mullerian duct develop to give the fallopian tube, uterus, and upper vagina.

10 Development of the External Genitalia:
The Phase of undifferentiated external genitalia Unlike the internal genitalia where there are two duct systems one for male and one for female, the external genitalia are derived from common anlagen: the genital tubercle, the genital swellings, and the genital folds that are capable of development into male or female genitalia under the influence of androgenic hormones produced by the Leydig cells of the testes.

11 Differentiation to male phenotype:
The testis begins secretion of testosterone by the 8-9th week; masculinization of the genitalia is observed about a week later (the 10th week) and is completed by the 14th week. However the target cells of the external genitalia must be able to convert testosterone to its active product Dihydrotestosterone (DHT) under the influence of the intracellular enzyme 5 alpha reductase

12 Differentiation to female phenotype:
In the absence of DHT the bipotential external genitalia differentiate into female

13 Migratory Path Of Primordial Germ Cells From The Yolk Sac
Along The Hindgut Mesentery, To The Urogenital Ridge At Approximately 5 Weeks

14 Indifferent Stage (Approximately 7 weeks)

15 Development of the external female genitalia
Approximately 10 weeks Approximately 12 weeks

16 PD: Paramesonephric duct
MD: Mesonephric Duct US: Urogenital Sinus MT: Mullerian Tubrcle UVP: Uterovaginal primordium VP: Vaginal plate

17 Remnants of the mesonephric (wolffian) ducts that may persist in the anterolateral vagina or adjacent to the uterus within the broad ligament or mesosalpinx.

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21 Bulging mass in a complete obstructive longitudinal vaginal septum

22 Rudimentary horn attached to the unicornuate uterus with a band of tissue. Dashed lines represent the dissection planes.

23 Rudimentary horn attached to the unicornuate uterus without intervening tissue. Dashed lines represent dissection planes.

24 a, Isolated congenital cervical atresia with normal vaginal development. b, Congenital cervical atresia with complete vaginal agenesis

25 Isolated congenital cervical atresia with normal vaginal development
Isolated congenital cervical atresia with normal vaginal development. b, Congenital cervical atresia with complete vaginal agenesis

26 Vaginal atresia.(From Sarto GE, Simpson JL: Abnormalities of müllerian and wolffian duct systems. Birth Defects: Original Article Series 14(6a):37, 1978.)

27 Potential sites of transverse vaginal septa. A. High septum. B
Potential sites of transverse vaginal septa. A. High septum. B. Midvaginal septum. C. Low septum.(From Simpson JL, Verp MS, Plouffe L Jr: Female genital system. In Stevenson RE, Hall JG, Goodman RM [eds]: Human Malformations and Related Anomalies, vol 11, pp 563–588. New York: Oxford University Press, 1993.)

28 Anomalies of the external genital organs Ambiguous Genitalia
Ambiguous Genitalia (Defect of the clitoris and labia):

29 Anomalies of the internal genital tract "Müllerian anomalies"
Normal development of the internal female genitalis (fallopian tubes, uterus, cervix, and the upper two thirds of the vagina) depends on three consecutive embryologic processes; first the differentiation of two paired mullerian ducts, second, lateral fusion of the lower segment of the mullerian ducts in the midline to form the uterus, cervix and upper two third of the vagina and finally resorption of the central septum between the two mullerian ducts in order to form a single uterine cavity and cervix.

30 In this classification four classes of Mullerian anomalies are identified; the two major ones are; disorders that compromise patency of the reproductive tract (obstructive mullerian anomalies) and disorders of lateral fusin of patent reproductive tract (longitudinal fusion anomalies). The remaining two classes are agenesis/hypoplasia (as in AFS class 1) and other miscellaneous anomalies that are difficult to classify

31 Obstructive Müllerian anomalies
transverse vaginal septa and cervical agenesis and dysgenesis with or without obstruction. Imperforate hymen is embryologically not of mullerian origin although clinically have a similar presentation. Patients with this type of anomaly will usually presents with amenorrhea or pain due to accumulated menstrual flow.

32 b) Imperforate Hymen: The hymen represents the junction of the sinovaginal bulbs with the urogenital sinus; hence it is formed form the endoderm of the urogenital sinus epithelium. An imperforate hymen may be discovered at birth because of the presence of a suprapubic mass "mucocolpos or hydrocolpos" More commonly however an imperforate hymen remains undetected until puberty when over time repeated accumulation of menstrual flow in the vagina produce a condition known as hematocolpos.

33 Defects of Mullerian Duct fusion:
Unlike obstructive anomalies that usually presents with primary amenorrhea, fusion anomalies are often associated with gynecological as well as obstetrics complications such as infertility, recurrent pregnancy loss and poor obstetrics outcome in pregnancy Some case where there is partial obstruction e.g. a unilateral rudimentary horn, may present early in the years following puberty usually with primary cyclic dysmenorrhea.

34 Anomalies of lateral fusion of the mullerian ducts: This may be partial or complete failure of fusion. Anomalies due to unilateral defects of Mullerian duct development: Diethylstilbestrol Associated anomalies:

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